Device Won Approval Though F.D.A. Staff Objected

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Device Won Approval Though F.D.A. Staff Objected

By GARDINER HARRIS

Published: February 17, 2006

WASHINGTON, Feb. 16 — A top federal medical official

overruled the unanimous opinion of his scientific

staff when he decided last year to approve a

pacemaker-like device to treat persistent depression,

a Senate committee reported Thursday.

The device, the surgically implanted vagus nerve

stimulator, had not proved effective against

depression in its only clinical trial for treatment of

that illness. As a result, scientists at the Food and

Drug Administration repeatedly and unanimously

recommended rejecting the application of its maker,

Cyberonics Inc., to sell it as such a treatment, said

the report, written by the staff of the Senate Finance

Committee.

But Dr. G. Schultz, director of the Center for

Devices and Radiological Health at the agency, kept

moving the application along and eventually decided to

approve it, the report said.

That approval did follow the backing of a divided

F.D.A. advisory committee. Still, the Senate

committee, which for two years has been investigating

the decision-making processes at the F.D.A., could

find no previous instance in which the director of the

center had approved a device in the face of unanimous

opposition from staff scientists and administrators

beneath him, the report said.

Dr. Schultz could not be reached for comment on

Thursday, but Bro, an F.D.A. spokeswoman, said

the device had been approved because many people with

persistent depression " are otherwise on their way to

institutionalization, because of the seriousness of

their illness. "

Ms. Bro said top officials did " occasionally overrule

staff recommendations after assessing all data, expert

opinion and medical need. "

Jill Gerber, a spokeswoman for Senator E.

Grassley, the Iowa Republican who heads the Senate

committee, said, " The report speaks for itself, and

Chairman Grassley has no additional comment. "

In a 1,900-word written response issued Thursday

night, P. Cummins, Cyberonics's chairman and

chief executive, said the investigators had failed to

interview many experts on serious depression.

Mr. Cummins said his company's device was " the only

safe and effective treatment option ever specifically

developed, studied, F.D.A.-approved and fully

informatively labeled for the treatment of chronic or

recurrent treatment-resistant depression. "

The vagus nerve stimulator is surgically implanted in

the upper chest, and its wires are threaded into the

neck. Batteries in the device stimulate a nerve

leading to the brain.

The nerve stimulator has been approved since 1997 for

the treatment of epilepsy in some patients. Common

side effects include voice alteration, increased

cough, shortness of breath, neck pain and difficulty

swallowing. The device has also been linked to rare

reports of death, heart problems and vocal cord

paralysis.

When some epilepsy patients reported that their moods

had changed after receiving the devices, Cyberonics,

based in Houston, implanted them in 235 depressed

patients and turned the machines on in half of them.

After three months, the two groups were equally

depressed. The trial had failed.

Cyberonics then turned the devices on in all 235

patients and determined that 30 percent showed

significant improvement after six months or more.

Without a control group, however, it was impossible to

determine if the device had caused the improvement.

Internal correspondence among F.D.A. reviewers shows

that some were bewildered by Dr. Schultz's support for

the device, the Senate report said.

" In my opinion, they do not have adequate data, and I

don't understand how this can move forward, " one

reviewer wrote in an e-mail message to a colleague,

the report said.

Another wrote, " As an M.D. interested in science, it

seems to me that such an approval would be akin to

approving an experimental product. "